- Bifunctional Br?nsted Base Catalyst Enables Regio-, Diastereo-, and Enantioselective Cα-Alkylation of β-Tetralones and Related Aromatic-Ring-Fused Cycloalkanones
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The catalytic asymmetric synthesis of both α-substituted and α,α-disubstituted (quaternary) β-tetralones through direct α-functionalization of the corresponding β-tetralone precursor remains elusive. A designed Br?nsted base-squaramide bifunctional catalyst promotes the conjugate addition of either unsubstituted or α-monosubstituted β-tetralones to nitroalkenes. Under these reaction conditions, not only enolization, and thus functionalization, occurs at the α-carbon atom of the β-tetralone exclusively, but adducts including all-carbon quaternary centers are also formed in highly diastereo- and enantioselective manner.
- Urruzuno, I?aki,Mugica, Odei,Oiarbide, Mikel,Palomo, Claudio
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supporting information
p. 2059 - 2063
(2017/02/15)
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- Synthesis and biological evaluation of compact, conformationally constrained bifunctional opioid agonist - Neurokinin-1 antagonist peptidomimetics
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A reported mixed opioid agonist - neurokinin 1 receptor (NK1R) antagonist 4 (Dmt-D-Arg-Aba-Gly-(3′,5′-(CF3)2)NMe-benzyl) was modified to identify important features in both pharmacophores. The new dual ligands were tested in vitro and subsequently two compounds (lead structure 4 and one of the new analogues 22, Dmt-D-Arg-Aba-β-Ala-NMe-Bn) were selected for in vivo behavioural assays, which were conducted in acute (tail-flick) and neuropathic pain models (cold plate and von Frey) in rats. Compared to the parent opioid compound 33 (without NK1R pharmacophore), hybrid 22 was more active in the neuropathic pain models. Attenuation of neuropathic pain emerged from NK1R antagonism as demonstrated by the pure NK1R antagonist 6. Surprisingly, despite a lower in vitro activity at NK1R in comparison with 4, compound 22 was more active in the neuropathic pain models. Although potent analgesic effects were observed for 4 and 22, upon chronic administration, both manifested a tolerance profile similar to that of morphine and cross tolerance with morphine in a neuropathic pain model in rat.
- Guillemyn, Karel,Kleczkowska, Patrycia,Lesniak, Anna,Dyniewicz, Jolanta,Van Der Poorten, Olivier,Van Den Eynde, Isabelle,Keresztes, Attila,Varga, Eva,Lai, Josephine,Porreca, Frank,Chung, Nga N.,Lemieux, Carole,Mika, Joanna,Rojewska, Ewelina,Makuch, Wioletta,Van Duppen, Joost,Przewlocka, Barbara,Vanden Broeck, Jozef,Lipkowski, Andrzej W.,Schiller, Peter W.,Tourwé, Dirk,Ballet, Steven
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- NOVEL NEUROKININ 1 RECEPTOR ANTAGONIST COMPOUNDS
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The present invention relates to a compound according to formula (A) wherein n is 1 or 2; R1 and R2 are independently hydrogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, CD3 or halogen; R3 is hydrogen, C(=O)OR7 or C1-4 alkyl optionally substituted with hyd
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Page/Page column 70; 71
(2013/09/12)
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- PROCESS FOR THE PREPARATION OF 3,5-BIS (TRIFLUOROMETHYL)-N-METHYLBENZYLAMINE
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The invention concerns a process for the preparation of 3,5-bis(trifluoromethyl)-N- methyl-benzylamine by means of an amino-dehalogenation reaction, more in particular starting from a 3,5-bis(trifluoromethyl)-benzyl halide, in particular starting from 3,5-bis(trifluoromethyl)-benzyl chloride and a new process for preparation of the latter.
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Page/Page column 6
(2008/06/13)
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- TACHYKININ RECEPTOR ANTAGONISTS
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The present invention relates to selective NK-1 receptor antagonists of Formula (I) or a pharmaceutically acceptable salt thereof, for the treatment of disorders associated with an excess of tachykinins.
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